Hydrogen bonded hydrogels

Abstract

The present invention relates to new hydrogel materials using water gellants that are comprised by hydrophilic polymers to which hydrogen bonding units are covalently attached. Optionally, the hydrogel contains additional ingredients or additives. These new reversible hydrogels can easily be fine-tuned in their mechanical performance and functionality and are especially suitable for cosmetic and biomedical applications.

1. A hydrogel composition comprising:
 (a) 0.3-50.0 wt. %, based on the total weight of the hydrogel composition, of a water gellant comprising a hydrophilic polymer to which at least two 4H-units are covalently attached, wherein the 4H-unit has the general formula (3) or formula (4) and tautomers thereof: 
 
       
         
           
           
               
               
           
         
         wherein X is nitrogen atom or a carbon atom bearing a substituent R 15 , and 
         wherein the 4H-unit is bonded to a polymer backbone via R 1  and R 2  or via R 1  and R 3  with the other R groups representing, independently a side chain according to (i)-(viii);
 (i) hydrogen; 
 (ii) C 1 -C 20  alkyl; 
 (iii) C 6 -C 12  aryl; 
 (iv) C 7 -C 12  alkaryl; 
 (v) C 7 -C 12  alkyl aryl; 
 (vi) polyester groups having the formula (5) 
 
       
       
         
           
           
               
               
           
         
         
           wherein R 4  and Y are independently selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl, n is 1-6 and m is 10 to 100; 
           (vii) C 1 -C 10  alkyl groups substituted with 1-4 ureido groups according to the formula (6):
   R 5 —NH—C(O)—NH—  (6)
 
 
           wherein R 5  is selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl; 
           (viii) polyether groups having the formula (7) 
         
       
       
         
           
           
               
               
           
         
         
           wherein R 6 , R 7  and Y are independently selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl and o is 10-100; 
         
         (b) 50.0 to 99.7 wt. % water, based on the total weight of hydrogel; 
         (c) a polar solvent other than water, wherein the polar solvent comprises less than 15 wt. % of the total weight of the hydrogel composition; and
 wherein components (a)-(c) form a hydrogel. 
 
       
     
     
       2. The hydrogel composition according to  claim 1 , wherein 2-50 4H-units are covalently attached to the hydrophilic polymer. 
     
     
       3. The hydrogel composition according to  claim 1 , wherein the water gellant is obtainable by functionalizing a hydrophilic homopolymer or a hydrophilic copolymer with 4H-units, independently selected from the group consisting of telechelic polymers, multifunctional polymers, functional star polymers, functional (hyper)branched polymers and functional dendritic polymers. 
     
     
       4. The hydrogel composition according to  claim 3 , wherein the water gellant derived from the multifunctional polymers has a number average molecular weight of 1200-1,000,000. 
     
     
       5. The hydrogel composition according to  claim 3 , wherein the water gellant derived from the telechelic polymers, the functional star polymers, the functional (hyper)branched polymers and the functional dendritic polymers has a number average molecular weight of 1200-100,000. 
     
     
       6. The hydrogel composition according to  claim 3 , wherein the water gellant derived from a block copolymer has a number average molecular weight of 1200-100,000. 
     
     
       7. The hydrogel composition according to  claim 1 , wherein the hydrophilic polymer is prepared from polymers obtainable by (co)polymerization of vinyl monomers, the vinyl monomers being selected from the group consisting of:
 (a) monomers according to the formula (8) 
 
       
         
           
           
               
               
           
         
         wherein R 8  is independently selected from the group consisting of: 
         (i) OH; 
         (ii) C 1 -C 12  linear or branched alkoxy, optionally substituted with 1-6 hydroxy groups; 
         (iii) amide according to the formula —N(R 10 ) 2  wherein R 10  can be hydrogen or C 1 -C 6  linear or branched alkyl, optionally substituted with 1-6 hydroxy groups; 
         (iv) ammonium salt according to the formula —[N(R 10 ) 3 ] + X − , wherein R 10  is as defined for (iii) and X is a halogen atom; and 
         (v) a group according to the formula (9) 
       
       
         
           
           
               
               
           
         
         wherein R 10  is as defined for (iii) and p is 1-50 and q=2 or 3; and 
         wherein R 9  is hydrogen or methyl; 
         (b) C 1 -C 12  linear or branched alkyl vinyl ether; 
         (c) vinyl alcohol; 
         (d) C 2 -C 12  α-alkenylene ω-sulfonate having an alkaline earth metal cation or an alkali metal cation; 
         (e) C 7 -C 12  vinylaryl sulfonate according to formula (10) 
       
       
         
           
           
               
               
           
         
         wherein R 10  is as defined for (iii) and M is an alkaline earth metal or an alkali metal cation; 
         CH 2 ═CH—R 11 , wherein R 11  is selected from the group consisting of pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyrrolidyl, indolyl, indolizinyl, indazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, phthalizinyl, naphtypyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, pyrrolidonyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, indolinyl, isoindolinyl, morpholinyl, isoxazolyl, furazinyl, and isothiazolyl; 
         (g) CH 2 ═CH—O—C(O)R 12 , wherein R 12  is selected from the group consisting of C 1 -C 6  linear or branched alkyl; 
         (h) CH 2 ═CH—CH 2 OR 13 , wherein R 13  is selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl; and 
         (i) N-vinyl lactams according to the formula (II) 
       
       
         
           
           
               
               
           
         
         wherein R 13  is as defined for (h) and r is 2-6. 
       
     
     
       8. The hydrogel composition according to  claim 1 , wherein the hydrophilic polymer is prepared from poly(ethylene oxide) polymers having OH end-groups according to formula (12):
   —[(CH 2 CH 2 O) r —H] s   (12)
 
 wherein r is in the range of 4 to 50 and s is in the range of 2 to 30. 
 
     
     
       9. The hydrogel composition according to  claim 1 , wherein the hydrophilic polymer is selected from the group consisting of polyethylene glycol having OH end-groups or poly(ethylene-co-propylene)glycol—random or block—having OH end-groups according to formula (13): 
       
         
           
           
               
               
           
         
         wherein R 14  is hydrogen or methyl and t is 20-100. 
       
     
     
       10. The hydrogel composition according to  claim 1 , wherein the hydrophilic polymer is selected from the group consisting of polyethylene glycol having OH end-groups or poly(ethylene-co-propylene) glycol—random or block—having OH end-groups according to formula (13) and wherein the hydrophilic polymer is additionally selected from the group consisting of polyesters and copolyesters having OH end-groups, or polycarbonates and copolycarbonates having OH end-groups, or polyorthoesters having OH end-groups. 
     
     
       11. The hydrogel composition according to  claim 1 , wherein the hydrogel comprises a biologically active or pharmaceutically active compound or a bioactive species. 
     
     
       12. The composition according to  claim 1 , wherein the 4H-unit is bonded to a polymer backbone via R 1  and R 3 . 
     
     
       13. The composition according to  claim 1 , wherein the polar solvent comprises less than 2 wt. % of the total weight of the hydrogel composition. 
     
     
       14. A pharmaceutical composition comprising:
 (a) 0.3-50.0 wt. %, based on the total weight of the pharmaceutical composition, of a water gellant comprising a hydrophilic polymer to which at least two 4H-units are covalently attached, wherein the 4H-unit has the general formula (3) or formula (4) and tautomers thereof: 
 
       
         
           
           
               
               
           
         
         wherein X is nitrogen atom or a carbon atom bearing a substituent R 15 , and 
         wherein the 4H-unit is bonded to a polymer backbone via R 1  and R 2  or via R 1  and R 3  with the other R groups representing, independently a side chain according to (i)-(viii);
 (i) hydrogen; 
 (ii) C 1 -C 20  alkyl; 
 (iii) C 6 -C 12  aryl; 
 (iv) C 7 -C 12  alkaryl; 
 (v) C 7 -C 12  alkyl aryl; 
 (vi) polyester groups having the formula (5) 
 
       
       
         
           
           
               
               
           
         
         
           wherein R 4  and Y are independently selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl, n is 1-6 and m is 10 to 100; 
           (vii) C 1 -C 10  alkyl groups substituted with 1-4 ureido groups according to the formula (6):
   R 5 —NH—C(O)—NH—  (6)
 
 
           wherein R 5  is selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl; 
           (viii) polyether groups having the formula (7) 
         
       
       
         
           
           
               
               
           
         
         
           wherein R 6 , R 7  and Y are independently selected from the group consisting of hydrogen and C 1 -C 6  linear or branched alkyl and o is 10-100; 
         
         (b) 50.0 to 99.7 wt. % water, based on the total weight of pharmaceutical composition; 
         (c) a polar solvent other than water, wherein the polar solvent comprises less than 2 wt. % of the total weight of hydrogel; 
         (d) a biologically active or pharmaceutically active compound or a bioactive species; and
 wherein components (a)-(d) form a hydrogel.